DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for diffuse gastric adenocarcinoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDiffuse gastric adenocarcinoma maps to a 46-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for diffuse gastric adenocarcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
MDM4 regulator of p53 (MDM4) — MDM4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 3~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6Q9Y · 1.2 Å · ligand 7-methoxy-~{N}-[(3~{S})-1-(4-methylphenyl)pyrrolidin-3-yl]-1~{H}-indole-3-carboxamide (HRQ). Experimental structure, not a prediction.
What the evidence adds up to
A SEER-based cohort study of 20,218 patients found that diffuse-type gastric adenocarcinoma had a poorer cancer-specific survival than the intestinal type (hazard ratio 1.44; 95% CI 1.38–1.50 on univariate analysis, and 1.20; 95% CI 1.15–1.20 after adjustment). After propensity score matching the hazard ratio was 1.23 (95% CI 1.10–1.36), and a competing risk model gave a subdistribution hazard ratio of 1.32 (95% CI 1.23–1.41). The survival difference disappeared for patients with T1 stage (HR 1.06; 95% CI 0.87–1.28) and tumour size <2 cm (HR 1.00; 95% CI 0.83–1.21).
A retrospective study of 125 patients with distal diffuse gastric cancer compared total gastrectomy with distal gastrectomy. Median overall survival was 89.0 months in the total gastrectomy group and 85.0 months in the distal gastrectomy group; 5-year overall survival was 60.3% (95% CI 0.460–0.791) versus 58.8% (95% CI 0.487–0.711). The difference was not statistically significant (p=0.75). However, intramural recurrence was higher after distal gastrectomy (12.7%, 8 of 63 patients) than after total gastrectomy (4.8%, 1 of 21 patients). The authors concluded that distal gastrectomy cannot be recommended as an alternative to total gastrectomy in patients with satisfactory functional status.
A small trial from 2014 randomised 25 patients with stage II or III gastric adenocarcinoma to neoadjuvant chemoradiotherapy (cisplatin and 5-fluorouracil with 45 Gy radiation) followed by surgery, or to surgery followed by adjuvant chemoradiotherapy. At 36 months, 2 of 12 patients (16.7%) in the neoadjuvant group and 5 of 13 (38.5%) in the adjuvant group were alive; the difference was not significant. Median survival was 13.4 months versus 21.6 months, also not significant. A 2010 retrospective study of 56 patients with metastatic or recurrent gastric adenocarcinoma found response rates of 43.3% for FOLFOX and 46.2% for FOLFIRI, with median time to progression of 4 months and 4.5 months, and median overall survival of 8.3 months versus 9.7 months (p=0.784). A 1993 review stated that multimodality therapy had not reproducibly improved survival, largely because staging was imprecise and regimens had only limited efficacy against advanced disease.
What is still missing are large, prospectively stratified trials that account for Lauren subtype and molecular behaviour, particularly for diffuse gastric adenocarcinoma. The existing data are retrospective, underpowered, or decades old, and no regimen has shown a clear survival advantage specific to the diffuse histology. Adequate funding for subtype-specific trials and better preoperative staging tools are needed before any treatment can be claimed to alter the natural history of this disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Translational Medicine · 2021 · 28 citations · open access
Differential prognostic implications of gastric adenocarcinoma based on Lauren’s classification: a Surveillance, Epidemiology, and End Results (SEER)-based cohort study
AbstractBACKGROUND: Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses. METHODS: According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis. RESULTS: After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21). CONCLUSIONS: Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type.
AbstractGastric adenocarcinoma is a complex disease that requires a thorough multidisciplinary approach for appropriate management. Management strategies vary in different regions of the world and have changed over time. In spite of improvements in chemotherapy and surgical techniques and an improvement in outcomes over the last several decades, overall survival remains low. The best outcomes are likely related to early detection, preoperative reduction of tumor burden with immunochemotherapy, consistent surgical technique for resection, and postoperative eradication of tumor cells. We aim to describe the management for gastric cancer, from the specifics of staging and imaging workup to the tenets of surgical resection and reconstruction as well as the adjuvant treatment strategies in this broad review of gastric cancer management.
Asian Pacific Journal of Cancer Prevention · 2014 · 6 citations · open access
Neoadjuvant Chemoradiotherapy in Non-cardia Gastric Cancer Patients - Does it Improve Survival?
AbstractBACKGROUND: Survival rates after resection of advanced gastric cancer are extremely poor. An increasing number of patients with gastric carcinomas (GC) are therefore being treated with preoperative chemotherapy. We evaluated 36 month survival rate of GC patients that were treated by adding a neoadjuvant chemoradiotherapy before gastrostomy. MATERIALS AND METHODS: Patients with stage II or III gastric adenocarcinomas were enrolled. The patients divided into two groups: (A) Neoadjuvant group that received concurrent chemoradiation before surgery (4,500 cGy of radiation at 180 cGy per day plus chemotherapy with cisplatin and 5-fluorouracil, in the first and the end four days of radiotherapy). Resection was attempted 5 to 6 weeks after end of chemoradiotherapy. (B) Adjuvant group that received concurrent chemo-radiation after surgical resection. RESULTS: Two (16.7%) patients out of 12 patients treated with neoadjuvant chemo-radiotherapy and 5 (38.5%) out of 13 in the surgery group survived after 36 months. These rates were not significantly different with per protocol and intention-to-treat analysis. The median survival time of patients in group A and B were 13.4 and 21.6 months , respectively, again not significantly different. Survival was significantly greater in patients with well differentiated adenocarcinoma in group B than in group A (p<0.004). CONCLUSIONS: According to this study we suggest surgery then chemoradiotherapy for patients with well differentiated gastric adenocarcinoma rather than other approaches. Additional studies with greater sample size and accurate matching relying on cancer molecular behavior are recommended.
Seminars in Surgical Oncology · 1993 · 5 citations
Efficacy of multimodality therapy in gastric adenocarcinoma
AbstractMultimodality therapy has not reproducibly improved the survival of patients with gastric adenocarcinoma. This is largely because the staging of disease has been imprecise and because the current regimens have only limited efficacy against advanced disease. Until staging is improved and active regimens are found, it will be difficult to identify synergism between surgery and other treatment modalities.
Korean Journal of Gastroenterology · 2010 · 5 citations · open access
Oxaliplatin and Leucovorin Plus Fluorouracil Versus Irinotecan and Leucovorin Plus Fluorouracil Combination Chemotherapy as a First-line Treatment in Patients with Metastatic or Recurred Gastric Adenocarcinoma
AbstractBACKGROUND/AIMS: We performed retrospective study in order to compare oxaliplatin, leucovorin, and fluorouracil (FOLFOX) versus irinotecan, leucovorin, and fluorouracil (FOLFIRI) in recurred or metastatic gastric adenocarcinoma. METHODS: We investigated 56 patients who were diagnosed with recurred or metastatic gastric adenocarcinoma in a single center during march, 2003 to march, 2008. The patients received either FOLFOX or FOLFIRI chemotherapy. RESULTS: There were no significant difference between the Oxaliplatin group (30 patients) and Irinotecan group (26 patients) in sex, age, and ECOG performance (p<0.05). Oxaliplatin group showed 1 case of CR (3.3%) and 12 cases of PR (40%), making the response rate 43.3%. Irinotecan group showed CR in 2 cases (7.7%) and PR in 10 cases (38.5%), making the response rate 46.2%. The median value of time to progression was 4 months in the oxlaplatin group and 4.5 months in the irinotecan group. The overall survival showed no significant difference (p=0.784), with the irinotecan group (9.7 months) being slightly longer than the Oxaliplatin group (8.3 months). Grade 3/4 neutropenia occurred similarly in both groups (4 cases in the oxalplatin group, 9 in the irinotecan group). CONCLUSIONS: Both combination treatment can be used safely and effectively in recurred or metastatic gastric adenocarcinoma.
Total gastrectomy (TG) versus distal gastrectomy (DG) for distal diffuse gastric cancer (GC).
Abstract305 Background: Diffuse gastric cancer (GC) in advanced stages has a poor prognosis. There is no clear consensus regarding the extent of surgical procedure for distal diffuse GC. Most surgeons prefer to perform total gastrectomy (TG) to achieve more radicality and reduce a local recurrence rate. Perhaps, the distal gastrectomy (DG) is not worse in terms of survival rates in distal diffuse GC compared with TG. Methods: The retrospective analysis was undertaken of 125 patients with distal diffuse gastric cancer. These patients received TG or DG at the N.N. Blokhin National Medical Research Center of Oncology in period from January 2005 to December 2022. We compared clinical, pathological features and survival rates between these groups. Results: Univariate analysis revealed that depth of tumor invasion, lymph nodes status and stage of the disease were associated with OS (p<0.05). Resection margin (R1) tended to be associated with OS (p=0.082). Multivariate analysis revealed that only stage of the disease was associated with OS (p<0.05). The median OS, 5-year OS in the DG group were 85,0 months, 58,8% (95% CI: 0.487-0.711). The median OS, 5-year OS in the TG group were 89,0 months, 60,3% (95% CI: 0.460-0.791). The differences in OS were not statistically significant between these groups (p=0.75). Such high overall survival rates were received because the 67,2% of patients had I-II stage of the disease. In our study only 84 patients were able to be followed-up after surgery: 63 (75%) in DG group and 21 (25%) in TG group. In the DG group intramural recurrence was detected in 12,7% of all cases of recurrence (8/63): 6 of them with intramural recurrence and 2 of them with synchronous intramural recurrence and distant metastasis. In the TG group intramural recurrence was detected only in one (4,8%) patient. Only 2 patients in DG group had R1-margin after primary surgery. Conclusions: DG for distal diffuse gastric cancer is associated with higher rate of intramural recurrence (12,7%) and cannot be recommended as an alternative to TG in patients with satisfactory functional status.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
